Chiral .alpha.-hydroxyketones are useful in the preparation of antimicrobials, for example: antifungals of the type described by Saji et al., "The 28th Interscience Conference on Antimicrobial Agents and Chemotherapy", Los Angeles, Oct. (1988), p. 140; and anti-fungal and anti-bacterials, such as: (+)-(2S,3S)-2-(2,4-difluoro-phenyl)-3-methylsulfonyl-1-(1,2,4-triazol-1-yl )-butan-2-ol and (-)-(2R,3R)-2-(2,4-difluorophenyl)-3-methylsulfonyl-1-(1,2,4-triazol-1-yl) -butan-2-ol, as disclosed by Konosu et al., Chem. Pharm. Bull. 1990, 38, 2476.
The preparation of chiral .alpha.-hydroxyketones and their derivatives by chemical methods is described in co-owned, co-pending U.S. application Ser. No. 07/676,042, filed Mar. 27, 1991. It is mainly by chemical methods that the literature teaches the synthesis of chiral .alpha.-hydroxyketones, e.g: Davis et al., J. Org. Chem., 1991, Vol. 56, pp 1143-1145; and Davis et al., J. Am. Chem. Soc., 1988, Vol. 110, pp. 8477-8482. However, Chenecert et al., Chemistry Letters, 1988, pp. 1191-1192, and Konishi et al., Chemistry Letters, 1985, pp. 1111-1112, show microbial synthesis of chiral .alpha.-hydroxyketones by reduction of diketones; and Matsumoto et al., Tetrahedron Lett. 1990, pp. 7163-7166, shows the enzymatic synthesis of chiral .alpha.-hydroxyketones by hydrolysis of enol esters.
Bianchi et al., Tetrahedron, 1989, Vol. 45, pp. 869-876, have shown that .alpha.-hydroxy aldehydes can be prepared by enzymatic hydrolysis of corresponding esters using lipases, such as from Pseudomonas species. However, the results obtained using aldehydes cannot be extrapolated to .alpha.-hydroxy ketones due to the greater steric effects inherent in the latter.
The asymmetric hydrolysis of .alpha.-acetoxyacylphenones by enzyme-mediated hydrolysis using a whole organism is disclosed by Ohta et al., Chem Letters, 1986, pp. 1169-1172 and by Yuki Gosei Yankuhin, in Japanese Patent Publication No. J6-2208298. Problems with the use of a whole organism include: low yields and/or slow reaction rates due to poor transport of the substrate or product across the cell membrane; poisoning of the organism by the substrate or the product; difficulties isolating the desired product from other products; and low yields due metabolism of the substrate or product through the action of other enzymes.